BOSTON – A reputedly neuroprotective compound will advance along its developmental pathway after developers said it exerted a blood level–dependent relationship with both cognitive and functional measures in patients with mild to moderate Alzheimer’s.

Most of the 26 patients left in the ongoing phase 2a extension study of ANAVEX 2-73 declined cognitively and functionally by varying degrees over 1 year. But a few, most of whom had high drug plasma levels, did experience cognitive and functional changes for the better. Some maintained stability, and some improved on both measures over 109 weeks, according to Christopher U. Missling, PhD, president and chief executive officer of Anavex.

“Improvement of cognition or function was a rare occurrence, but our analysis showed that patients who had a plasma concentration of 4-12 ng/mL had the best chance of experiencing this,” Dr. Missling said in an interview.

Mohammad Afshar, MD, PhD, presented these data at the Clinical Trials in Alzheimer’s Disease conference. He is the head of Ariana Pharmaceuticals, a firm hired to perform an independent analysis of the Anavex data. Concentrating on the pharmacodynamics data, he said ANAVEX 2-73 exhibits a clear drug concentration–clinical response relationship, which supports taking the drug into a phase 2/3 study.

“When focusing on the best responders at week 57, they continued to perform well. Patients with a score of greater than 20 on the Mini-Mental State Exam at baseline tended to respond better, as well as those with the highest plasma concentration,” he said.

The concentration-response picture is not completely clear, however. While five patients with high levels did improve on the MMSE at 57 weeks, one patient with a low plasma level also improved, and four patients with high levels declined. Functional results appeared more clearly related to drug levels: All of the high-level patients except one improved, as did about half of those with moderate plasma levels. Everyone with a low level declined.

During a later interview, Dr. Missling reviewed the data with an eye toward understatement. The study’s primary endpoints are safety and tolerability, as well as dosing and pharmacokinetics, he noted – cognitive and functional endpoints are exploratory measures. The study never had a control arm, other than several historical cohorts that served as reference points for decline in typically managed Alzheimer’s patients. And of course, he said, the numbers are very, very small.

Dr. Missling said ANAVEX 2-73 still appears safe and well tolerated. In the initial study phase, 98% of the subjects did have an adverse event; only one was considered serious. This was a case of delirium that developed in a patient who had several risk factors for the disorder, including a prior episode, and was not considered related to the study drug. Three patients withdrew because of an adverse event in the first 57 weeks; no one has withdrawn because of a side effect since then.

Dizziness was the most common adverse event (20 incidents in 15 patients), followed by headache (16 in 10 patients). Most (94%) occurred in the first week of treatment. All were mild or moderate. Headache and dizziness are considered signs that patients are approaching their maximum tolerated dose, Dr. Missling said.

The company’s task now is to find a standard minimum dose that is strong enough to get patients to at least 4 ng/mL plasma level, without inducing these side effects. The extension study will close out in November 2018. Anavex hopes to begin the drug’s next phase of development before then, with a phase 2/3 study of about 200 patients.

“We’re trying to gather as much data as possible so we can do this properly,” Dr. Missling said. “You can make the case that some developers have rushed into these studies after interpreting early results the wrong way. They said the glass was half-full when it was really half-empty. For us, it’s very important not to do that. We won’t go ahead with this until we are completely comfortable with what we see.”

[email protected]

On Twitter @alz_gal

BOSTON – A reputedly neuroprotective compound will advance along its developmental pathway after developers said it exerted a blood level–dependent relationship with both cognitive and functional measures in patients with mild to moderate Alzheimer’s.

Most of the 26 patients left in the ongoing phase 2a extension study of ANAVEX 2-73 declined cognitively and functionally by varying degrees over 1 year. But a few, most of whom had high drug plasma levels, did experience cognitive and functional changes for the better. Some maintained stability, and some improved on both measures over 109 weeks, according to Christopher U. Missling, PhD, president and chief executive officer of Anavex.

“Improvement of cognition or function was a rare occurrence, but our analysis showed that patients who had a plasma concentration of 4-12 ng/mL had the best chance of experiencing this,” Dr. Missling said in an interview.

Mohammad Afshar, MD, PhD, presented these data at the Clinical Trials in Alzheimer’s Disease conference. He is the head of Ariana Pharmaceuticals, a firm hired to perform an independent analysis of the Anavex data. Concentrating on the pharmacodynamics data, he said ANAVEX 2-73 exhibits a clear drug concentration–clinical response relationship, which supports taking the drug into a phase 2/3 study.

“When focusing on the best responders at week 57, they continued to perform well. Patients with a score of greater than 20 on the Mini-Mental State Exam at baseline tended to respond better, as well as those with the highest plasma concentration,” he said.

The concentration-response picture is not completely clear, however. While five patients with high levels did improve on the MMSE at 57 weeks, one patient with a low plasma level also improved, and four patients with high levels declined. Functional results appeared more clearly related to drug levels: All of the high-level patients except one improved, as did about half of those with moderate plasma levels. Everyone with a low level declined.

During a later interview, Dr. Missling reviewed the data with an eye toward understatement. The study’s primary endpoints are safety and tolerability, as well as dosing and pharmacokinetics, he noted – cognitive and functional endpoints are exploratory measures. The study never had a control arm, other than several historical cohorts that served as reference points for decline in typically managed Alzheimer’s patients. And of course, he said, the numbers are very, very small.

Dr. Missling said ANAVEX 2-73 still appears safe and well tolerated. In the initial study phase, 98% of the subjects did have an adverse event; only one was considered serious. This was a case of delirium that developed in a patient who had several risk factors for the disorder, including a prior episode, and was not considered related to the study drug. Three patients withdrew because of an adverse event in the first 57 weeks; no one has withdrawn because of a side effect since then.

Dizziness was the most common adverse event (20 incidents in 15 patients), followed by headache (16 in 10 patients). Most (94%) occurred in the first week of treatment. All were mild or moderate. Headache and dizziness are considered signs that patients are approaching their maximum tolerated dose, Dr. Missling said.

The company’s task now is to find a standard minimum dose that is strong enough to get patients to at least 4 ng/mL plasma level, without inducing these side effects. The extension study will close out in November 2018. Anavex hopes to begin the drug’s next phase of development before then, with a phase 2/3 study of about 200 patients.

“We’re trying to gather as much data as possible so we can do this properly,” Dr. Missling said. “You can make the case that some developers have rushed into these studies after interpreting early results the wrong way. They said the glass was half-full when it was really half-empty. For us, it’s very important not to do that. We won’t go ahead with this until we are completely comfortable with what we see.”

[email protected]

On Twitter @alz_gal

BOSTON – A reputedly neuroprotective compound will advance along its developmental pathway after developers said it exerted a blood level–dependent relationship with both cognitive and functional measures in patients with mild to moderate Alzheimer’s.

Most of the 26 patients left in the ongoing phase 2a extension study of ANAVEX 2-73 declined cognitively and functionally by varying degrees over 1 year. But a few, most of whom had high drug plasma levels, did experience cognitive and functional changes for the better. Some maintained stability, and some improved on both measures over 109 weeks, according to Christopher U. Missling, PhD, president and chief executive officer of Anavex.

“Improvement of cognition or function was a rare occurrence, but our analysis showed that patients who had a plasma concentration of 4-12 ng/mL had the best chance of experiencing this,” Dr. Missling said in an interview.

Mohammad Afshar, MD, PhD, presented these data at the Clinical Trials in Alzheimer’s Disease conference. He is the head of Ariana Pharmaceuticals, a firm hired to perform an independent analysis of the Anavex data. Concentrating on the pharmacodynamics data, he said ANAVEX 2-73 exhibits a clear drug concentration–clinical response relationship, which supports taking the drug into a phase 2/3 study.

“When focusing on the best responders at week 57, they continued to perform well. Patients with a score of greater than 20 on the Mini-Mental State Exam at baseline tended to respond better, as well as those with the highest plasma concentration,” he said.

The concentration-response picture is not completely clear, however. While five patients with high levels did improve on the MMSE at 57 weeks, one patient with a low plasma level also improved, and four patients with high levels declined. Functional results appeared more clearly related to drug levels: All of the high-level patients except one improved, as did about half of those with moderate plasma levels. Everyone with a low level declined.

During a later interview, Dr. Missling reviewed the data with an eye toward understatement. The study’s primary endpoints are safety and tolerability, as well as dosing and pharmacokinetics, he noted – cognitive and functional endpoints are exploratory measures. The study never had a control arm, other than several historical cohorts that served as reference points for decline in typically managed Alzheimer’s patients. And of course, he said, the numbers are very, very small.

Dr. Missling said ANAVEX 2-73 still appears safe and well tolerated. In the initial study phase, 98% of the subjects did have an adverse event; only one was considered serious. This was a case of delirium that developed in a patient who had several risk factors for the disorder, including a prior episode, and was not considered related to the study drug. Three patients withdrew because of an adverse event in the first 57 weeks; no one has withdrawn because of a side effect since then.

Dizziness was the most common adverse event (20 incidents in 15 patients), followed by headache (16 in 10 patients). Most (94%) occurred in the first week of treatment. All were mild or moderate. Headache and dizziness are considered signs that patients are approaching their maximum tolerated dose, Dr. Missling said.

The company’s task now is to find a standard minimum dose that is strong enough to get patients to at least 4 ng/mL plasma level, without inducing these side effects. The extension study will close out in November 2018. Anavex hopes to begin the drug’s next phase of development before then, with a phase 2/3 study of about 200 patients.

“We’re trying to gather as much data as possible so we can do this properly,” Dr. Missling said. “You can make the case that some developers have rushed into these studies after interpreting early results the wrong way. They said the glass was half-full when it was really half-empty. For us, it’s very important not to do that. We won’t go ahead with this until we are completely comfortable with what we see.”

[email protected]

On Twitter @alz_gal

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

This is the fourth in a series of articles from the National Center for Excellence in Primary Care Research (NCEPCR) in the Agency for Healthcare Research and Quality (AHRQ). This series introduces sets of tools and resources designed to help your practice.

Many patients with anxiety, depression, behavioral problems, substance abuse, and other mental and behavioral health conditions turn to their primary care providers as their first, and often only, source of mental health care. Unfortunately, this care may not be as effective as patients and primary care personnel would hope or expect it to be. Problems exist with missed or inaccurate diagnoses, referrals and coordination of care, and other failures in detection and treatment (NIMH Integrated Care Web site, accessed Oct. 1, 2017).

Links from the NCEPCR site:

Tools and Resources for Research, Quality Improvement, and Practice

https://www.ahrq.gov/ncepcr/research-qi-practice/practice-transformation-qi.html

Academy Web Portal: https://www.integrationacademy.ahrq.gov

The Integration Playbook: https://integrationacademy.ahrq.gov/playbook/about-playbook

Lexicon: https://integrationacademy.ahrq.gov/lexicon

Atlas of Integrated Behavioral Health Care Quality Measures: https://integrationacademy.ahrq.gov/resources/ibhc-measures-atlas

These and other tools can be found at the NCEPCR Web site: https://www.ahrq.gov/ncepcr.

Dr. Genevro is a health scientist at AHRQ. Dr. Ganiats is director, National Center for Excellence in Primary Care Research, AHRQ.

This is the fourth in a series of articles from the National Center for Excellence in Primary Care Research (NCEPCR) in the Agency for Healthcare Research and Quality (AHRQ). This series introduces sets of tools and resources designed to help your practice.

Many patients with anxiety, depression, behavioral problems, substance abuse, and other mental and behavioral health conditions turn to their primary care providers as their first, and often only, source of mental health care. Unfortunately, this care may not be as effective as patients and primary care personnel would hope or expect it to be. Problems exist with missed or inaccurate diagnoses, referrals and coordination of care, and other failures in detection and treatment (NIMH Integrated Care Web site, accessed Oct. 1, 2017).

Links from the NCEPCR site:

Tools and Resources for Research, Quality Improvement, and Practice

https://www.ahrq.gov/ncepcr/research-qi-practice/practice-transformation-qi.html

Academy Web Portal: https://www.integrationacademy.ahrq.gov

The Integration Playbook: https://integrationacademy.ahrq.gov/playbook/about-playbook

Lexicon: https://integrationacademy.ahrq.gov/lexicon

Atlas of Integrated Behavioral Health Care Quality Measures: https://integrationacademy.ahrq.gov/resources/ibhc-measures-atlas

These and other tools can be found at the NCEPCR Web site: https://www.ahrq.gov/ncepcr.

Dr. Genevro is a health scientist at AHRQ. Dr. Ganiats is director, National Center for Excellence in Primary Care Research, AHRQ.

This is the fourth in a series of articles from the National Center for Excellence in Primary Care Research (NCEPCR) in the Agency for Healthcare Research and Quality (AHRQ). This series introduces sets of tools and resources designed to help your practice.

Many patients with anxiety, depression, behavioral problems, substance abuse, and other mental and behavioral health conditions turn to their primary care providers as their first, and often only, source of mental health care. Unfortunately, this care may not be as effective as patients and primary care personnel would hope or expect it to be. Problems exist with missed or inaccurate diagnoses, referrals and coordination of care, and other failures in detection and treatment (NIMH Integrated Care Web site, accessed Oct. 1, 2017).

Links from the NCEPCR site:

Tools and Resources for Research, Quality Improvement, and Practice

https://www.ahrq.gov/ncepcr/research-qi-practice/practice-transformation-qi.html

Academy Web Portal: https://www.integrationacademy.ahrq.gov

The Integration Playbook: https://integrationacademy.ahrq.gov/playbook/about-playbook

Lexicon: https://integrationacademy.ahrq.gov/lexicon

Atlas of Integrated Behavioral Health Care Quality Measures: https://integrationacademy.ahrq.gov/resources/ibhc-measures-atlas

These and other tools can be found at the NCEPCR Web site: https://www.ahrq.gov/ncepcr.

Dr. Genevro is a health scientist at AHRQ. Dr. Ganiats is director, National Center for Excellence in Primary Care Research, AHRQ.

BACKGROUND AND OBJECTIVES: Adherence to American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline recommendations improved significantly through the AAP’s multi-institutional collaborative the Bronchiolitis Quality Improvement Project (BQIP). We assessed sustainability of improvements at participating institutions for 1 year following completion of the collaborative.

METHODS: Twenty-one multidisciplinary hospital-based teams provided monthly data for key inpatient bronchiolitis measures during baseline and intervention bronchiolitis seasons. Nine sites provided data in the season following completion of the collaborative. Encounters included children younger than 24 months who were hospitalized for bronchiolitis without comorbid chronic illness, prematurity, or intensive care. Changes between baseline-, intervention-, and sustainability-season data were assessed using generalized linear mixed-effects models with site-specific random effects. Differences between hospital characteristics, baseline performance, and initial improvement among sites that did and did not participate in the sustainability season were compared.

RESULTS: A total of 2,275 discharges were reviewed, comprising 995 baseline, 877 intervention, and 403 sustainability-season encounters. Improvements in all key bronchiolitis quality measures achieved during the intervention season were maintained during the sustainability season, and orders for intermittent pulse oximetry increased from 40.6% (95% confidence interval, 22.8-61.1) to 79.2% (95% CI, 58.0-91.3). Sites that did and did not participate in the sustainability season had similar characteristics.

DISCUSSION: BQIP participating sites maintained improvements in key bronchiolitis quality measures for 1 year following the project’s completion. This approach, which provided an evidence-based best-practice toolkit while building the quality-improvement capacity of local interdisciplinary teams, may support performance gains that persist beyond the active phase of the collaborative.
 

Also in JHM this month

The effect of an inpatient smoking cessation treatment program on hospital readmissions and length of stayAUTHORS: Eline M. van den Broek-Altenburg, MS, MA, Adam J. Atherly, PhD

Treatment trends and outcomes in healthcare-associated pneumoniaAUTHORS: Sarah Haessler, MD; Tara Lagu, MD, MPH; Peter K. Lindenauer, MD, MSc; Daniel J. Skiest, MD; Aruna Priya, MA, MSc; Penelope S. Pekow, PhD; Marya D. Zilberberg, MD, MPH; Thomas L. Higgins, MD, MBA; Michael B. Rothberg, MD, MPH

What’s the purpose of rounds? A qualitative study examining the perceptions of faculty and studentsAUTHORS: Oliver Hulland; Jeanne Farnan, MD, MHPE; Raphael Rabinowitz; Lisa Kearns, MD, MS; Michele Long, MD; Bradley Monash, MD; Priti Bhansali, MD; H. Barrett Fromme, MD, MHPE

Association between anemia and fatigue in hospitalized patients: does the measure of anemia matter?AUTHORS: Micah T. Prochaska, MD, MS; Richard Newcomb, BA; Graham Block, BA; Brian Park, BA; David O. Meltzer MD, PhD

Helping seniors plan for posthospital discharge needs before a hospitalization occurs: Results from the randomized control trial of planyourlifespan.orgAUTHORS: Lee A. Lindquist, MD, MPH, MBA; Vanessa Ramirez-Zohfeld, MPH; Priya D. Sunkara, MA; Chris Forcucci, RN, BSN; Dianne S. Campbell, BS; Phyllis Mitzen, MA; Jody D. Ciolino, PhD; Gayle Kricke, MSW; Anne Seltzer, LSW; Ana V. Ramirez, BA; Kenzie A. Cameron, PhD, MPH

BACKGROUND AND OBJECTIVES: Adherence to American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline recommendations improved significantly through the AAP’s multi-institutional collaborative the Bronchiolitis Quality Improvement Project (BQIP). We assessed sustainability of improvements at participating institutions for 1 year following completion of the collaborative.

METHODS: Twenty-one multidisciplinary hospital-based teams provided monthly data for key inpatient bronchiolitis measures during baseline and intervention bronchiolitis seasons. Nine sites provided data in the season following completion of the collaborative. Encounters included children younger than 24 months who were hospitalized for bronchiolitis without comorbid chronic illness, prematurity, or intensive care. Changes between baseline-, intervention-, and sustainability-season data were assessed using generalized linear mixed-effects models with site-specific random effects. Differences between hospital characteristics, baseline performance, and initial improvement among sites that did and did not participate in the sustainability season were compared.

RESULTS: A total of 2,275 discharges were reviewed, comprising 995 baseline, 877 intervention, and 403 sustainability-season encounters. Improvements in all key bronchiolitis quality measures achieved during the intervention season were maintained during the sustainability season, and orders for intermittent pulse oximetry increased from 40.6% (95% confidence interval, 22.8-61.1) to 79.2% (95% CI, 58.0-91.3). Sites that did and did not participate in the sustainability season had similar characteristics.

DISCUSSION: BQIP participating sites maintained improvements in key bronchiolitis quality measures for 1 year following the project’s completion. This approach, which provided an evidence-based best-practice toolkit while building the quality-improvement capacity of local interdisciplinary teams, may support performance gains that persist beyond the active phase of the collaborative.
 

Also in JHM this month

The effect of an inpatient smoking cessation treatment program on hospital readmissions and length of stayAUTHORS: Eline M. van den Broek-Altenburg, MS, MA, Adam J. Atherly, PhD

Treatment trends and outcomes in healthcare-associated pneumoniaAUTHORS: Sarah Haessler, MD; Tara Lagu, MD, MPH; Peter K. Lindenauer, MD, MSc; Daniel J. Skiest, MD; Aruna Priya, MA, MSc; Penelope S. Pekow, PhD; Marya D. Zilberberg, MD, MPH; Thomas L. Higgins, MD, MBA; Michael B. Rothberg, MD, MPH

What’s the purpose of rounds? A qualitative study examining the perceptions of faculty and studentsAUTHORS: Oliver Hulland; Jeanne Farnan, MD, MHPE; Raphael Rabinowitz; Lisa Kearns, MD, MS; Michele Long, MD; Bradley Monash, MD; Priti Bhansali, MD; H. Barrett Fromme, MD, MHPE

Association between anemia and fatigue in hospitalized patients: does the measure of anemia matter?AUTHORS: Micah T. Prochaska, MD, MS; Richard Newcomb, BA; Graham Block, BA; Brian Park, BA; David O. Meltzer MD, PhD

Helping seniors plan for posthospital discharge needs before a hospitalization occurs: Results from the randomized control trial of planyourlifespan.orgAUTHORS: Lee A. Lindquist, MD, MPH, MBA; Vanessa Ramirez-Zohfeld, MPH; Priya D. Sunkara, MA; Chris Forcucci, RN, BSN; Dianne S. Campbell, BS; Phyllis Mitzen, MA; Jody D. Ciolino, PhD; Gayle Kricke, MSW; Anne Seltzer, LSW; Ana V. Ramirez, BA; Kenzie A. Cameron, PhD, MPH

BACKGROUND AND OBJECTIVES: Adherence to American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline recommendations improved significantly through the AAP’s multi-institutional collaborative the Bronchiolitis Quality Improvement Project (BQIP). We assessed sustainability of improvements at participating institutions for 1 year following completion of the collaborative.

METHODS: Twenty-one multidisciplinary hospital-based teams provided monthly data for key inpatient bronchiolitis measures during baseline and intervention bronchiolitis seasons. Nine sites provided data in the season following completion of the collaborative. Encounters included children younger than 24 months who were hospitalized for bronchiolitis without comorbid chronic illness, prematurity, or intensive care. Changes between baseline-, intervention-, and sustainability-season data were assessed using generalized linear mixed-effects models with site-specific random effects. Differences between hospital characteristics, baseline performance, and initial improvement among sites that did and did not participate in the sustainability season were compared.

RESULTS: A total of 2,275 discharges were reviewed, comprising 995 baseline, 877 intervention, and 403 sustainability-season encounters. Improvements in all key bronchiolitis quality measures achieved during the intervention season were maintained during the sustainability season, and orders for intermittent pulse oximetry increased from 40.6% (95% confidence interval, 22.8-61.1) to 79.2% (95% CI, 58.0-91.3). Sites that did and did not participate in the sustainability season had similar characteristics.

DISCUSSION: BQIP participating sites maintained improvements in key bronchiolitis quality measures for 1 year following the project’s completion. This approach, which provided an evidence-based best-practice toolkit while building the quality-improvement capacity of local interdisciplinary teams, may support performance gains that persist beyond the active phase of the collaborative.
 

Also in JHM this month

The effect of an inpatient smoking cessation treatment program on hospital readmissions and length of stayAUTHORS: Eline M. van den Broek-Altenburg, MS, MA, Adam J. Atherly, PhD

Treatment trends and outcomes in healthcare-associated pneumoniaAUTHORS: Sarah Haessler, MD; Tara Lagu, MD, MPH; Peter K. Lindenauer, MD, MSc; Daniel J. Skiest, MD; Aruna Priya, MA, MSc; Penelope S. Pekow, PhD; Marya D. Zilberberg, MD, MPH; Thomas L. Higgins, MD, MBA; Michael B. Rothberg, MD, MPH

What’s the purpose of rounds? A qualitative study examining the perceptions of faculty and studentsAUTHORS: Oliver Hulland; Jeanne Farnan, MD, MHPE; Raphael Rabinowitz; Lisa Kearns, MD, MS; Michele Long, MD; Bradley Monash, MD; Priti Bhansali, MD; H. Barrett Fromme, MD, MHPE

Association between anemia and fatigue in hospitalized patients: does the measure of anemia matter?AUTHORS: Micah T. Prochaska, MD, MS; Richard Newcomb, BA; Graham Block, BA; Brian Park, BA; David O. Meltzer MD, PhD

Helping seniors plan for posthospital discharge needs before a hospitalization occurs: Results from the randomized control trial of planyourlifespan.orgAUTHORS: Lee A. Lindquist, MD, MPH, MBA; Vanessa Ramirez-Zohfeld, MPH; Priya D. Sunkara, MA; Chris Forcucci, RN, BSN; Dianne S. Campbell, BS; Phyllis Mitzen, MA; Jody D. Ciolino, PhD; Gayle Kricke, MSW; Anne Seltzer, LSW; Ana V. Ramirez, BA; Kenzie A. Cameron, PhD, MPH

MONTREAL – Female family physicians report more burnout and fewer self-care activities than their male colleagues, according to the results of a survey that found a significant gender divide in physician wellness.

Female respondents to the Texas-wide electronic survey of practicing physicians and residents reported more emotional exhaustion (P = .004) and higher levels of work stress (P = .009) than their male colleagues. Additionally, they reported sleeping less (P = .009), exercising less (P = .001), and eating healthy food less often (P = .005).

shutteratakan/Thinkstock

[email protected]

On Twitter @karioakes

MONTREAL – Female family physicians report more burnout and fewer self-care activities than their male colleagues, according to the results of a survey that found a significant gender divide in physician wellness.

Female respondents to the Texas-wide electronic survey of practicing physicians and residents reported more emotional exhaustion (P = .004) and higher levels of work stress (P = .009) than their male colleagues. Additionally, they reported sleeping less (P = .009), exercising less (P = .001), and eating healthy food less often (P = .005).

shutteratakan/Thinkstock

[email protected]

On Twitter @karioakes

MONTREAL – Female family physicians report more burnout and fewer self-care activities than their male colleagues, according to the results of a survey that found a significant gender divide in physician wellness.

Female respondents to the Texas-wide electronic survey of practicing physicians and residents reported more emotional exhaustion (P = .004) and higher levels of work stress (P = .009) than their male colleagues. Additionally, they reported sleeping less (P = .009), exercising less (P = .001), and eating healthy food less often (P = .005).

shutteratakan/Thinkstock

[email protected]

On Twitter @karioakes

Four to six cycles of bendamustine/rituximab is the primary regimen of choice for symptomatic, treatment-naive patients with Waldenström macroglobulinemia, especially when rapid control is needed for bulky disease, according to treatment guidelines from a multidisciplinary expert panel.

The Mayo Clinic Cancer Center Myeloma, Amyloidosis, and Dysproteinemia and Lymphoma Disease-Oriented Groups, composed of experts who have collectively treated hundreds of patients with Waldenström macroglobulinemia, updated their recommendations for management of the condition in JAMA Oncology. It’s the first update from the group since 2010. The new treatment approaches are based on clinical and observational studies published or presented through December 2015 and consensus recommendations.

The Mayo group said dexamethasone-rituximab-cyclophosphamide can be an alternative treatment for patients with symptomatic Waldenström macroglobulinemia with a low disease burden. But because of an absence of data, the group said rituximab maintenance therapy is not recommended for routine use outside of clinical trials.

Rituximab monotherapy is contraindicated if patients have symptomatic hyperviscosity; without preemptive plasmapheresis, this treatment should be avoided in those with very high serum IgM. They recommended a prompt start of therapeutic plasma exchange for hyperviscosity syndrome, before starting cytoreductive treatment. But rituximab is indicated when patients have symptomatic mild to moderate anemia, symptomatic cryoglobulinemia (in combination with steroids), or hemolytic anemia that does not respond to corticosteroids.

In cases of first or second relapse, autologous stem cell transplantation should be considered in patients with chemosensitive disease who are eligible for transplant, especially when the first remission duration was less than 2 years. Patients with refractory Waldenström macroglobulinemia should not be offered autologous stem cell transplantation.

Read the full set of recommendations in JAMA Oncology (2017 Sep 1;3[9]:1257-65).

[email protected]

On Twitter @maryellenny

Four to six cycles of bendamustine/rituximab is the primary regimen of choice for symptomatic, treatment-naive patients with Waldenström macroglobulinemia, especially when rapid control is needed for bulky disease, according to treatment guidelines from a multidisciplinary expert panel.

The Mayo Clinic Cancer Center Myeloma, Amyloidosis, and Dysproteinemia and Lymphoma Disease-Oriented Groups, composed of experts who have collectively treated hundreds of patients with Waldenström macroglobulinemia, updated their recommendations for management of the condition in JAMA Oncology. It’s the first update from the group since 2010. The new treatment approaches are based on clinical and observational studies published or presented through December 2015 and consensus recommendations.

The Mayo group said dexamethasone-rituximab-cyclophosphamide can be an alternative treatment for patients with symptomatic Waldenström macroglobulinemia with a low disease burden. But because of an absence of data, the group said rituximab maintenance therapy is not recommended for routine use outside of clinical trials.

Rituximab monotherapy is contraindicated if patients have symptomatic hyperviscosity; without preemptive plasmapheresis, this treatment should be avoided in those with very high serum IgM. They recommended a prompt start of therapeutic plasma exchange for hyperviscosity syndrome, before starting cytoreductive treatment. But rituximab is indicated when patients have symptomatic mild to moderate anemia, symptomatic cryoglobulinemia (in combination with steroids), or hemolytic anemia that does not respond to corticosteroids.

In cases of first or second relapse, autologous stem cell transplantation should be considered in patients with chemosensitive disease who are eligible for transplant, especially when the first remission duration was less than 2 years. Patients with refractory Waldenström macroglobulinemia should not be offered autologous stem cell transplantation.

Read the full set of recommendations in JAMA Oncology (2017 Sep 1;3[9]:1257-65).

[email protected]

On Twitter @maryellenny

Four to six cycles of bendamustine/rituximab is the primary regimen of choice for symptomatic, treatment-naive patients with Waldenström macroglobulinemia, especially when rapid control is needed for bulky disease, according to treatment guidelines from a multidisciplinary expert panel.

The Mayo Clinic Cancer Center Myeloma, Amyloidosis, and Dysproteinemia and Lymphoma Disease-Oriented Groups, composed of experts who have collectively treated hundreds of patients with Waldenström macroglobulinemia, updated their recommendations for management of the condition in JAMA Oncology. It’s the first update from the group since 2010. The new treatment approaches are based on clinical and observational studies published or presented through December 2015 and consensus recommendations.

The Mayo group said dexamethasone-rituximab-cyclophosphamide can be an alternative treatment for patients with symptomatic Waldenström macroglobulinemia with a low disease burden. But because of an absence of data, the group said rituximab maintenance therapy is not recommended for routine use outside of clinical trials.

Rituximab monotherapy is contraindicated if patients have symptomatic hyperviscosity; without preemptive plasmapheresis, this treatment should be avoided in those with very high serum IgM. They recommended a prompt start of therapeutic plasma exchange for hyperviscosity syndrome, before starting cytoreductive treatment. But rituximab is indicated when patients have symptomatic mild to moderate anemia, symptomatic cryoglobulinemia (in combination with steroids), or hemolytic anemia that does not respond to corticosteroids.

In cases of first or second relapse, autologous stem cell transplantation should be considered in patients with chemosensitive disease who are eligible for transplant, especially when the first remission duration was less than 2 years. Patients with refractory Waldenström macroglobulinemia should not be offered autologous stem cell transplantation.

Read the full set of recommendations in JAMA Oncology (2017 Sep 1;3[9]:1257-65).

[email protected]

On Twitter @maryellenny

CHICAGO – Screening mothers for postpartum depression is critical, because of the potential negative consequences for the child, according to Nerissa S. Bauer, MD, MPH.

Postpartum depression is the best known mood disorder related to pregnancy, but it’s not the only one. Perinatal mood and anxiety disorders exist along a spectrum, she told attendees at the American Academy of Pediatrics annual meeting. That spectrum includes prenatal depression, prenatal anxiety, “baby blues,” postpartum depression, posttraumatic stress disorder (PSTD), and postpartum anxiety with panic attacks and/or obsessive-compulsive disorder (OCD).

monkeybusinessimages/Thinkstock

Postpartum mood disorders

Postpartum depression (PPD), however, is serious and requires intervention. An estimated 10%-20% of new mothers experience PPD, but the numbers are much higher in at-risk communities. Up to 48% of mothers in low-income households and 40%-60% of adolescent mothers in low-income households experience it. Yet only about 15% of these higher-risk women seek treatment for PPD (Pediatrics. 2010 Nov;126[5]:1032-9).

PPD symptoms are similar to the usual symptoms of a depressive disorder: depressed mood, irritability, changes in sleep and/or appetite, fatigue, sleepiness, loss of interest in activities, inability to feel pleasure in everyday life, guilt, difficulty concentrating, indecisiveness, low energy, despair, and feelings of worthlessness. The biggest difference – and most important symptom – is that women with PPD may have thoughts about harming not only themselves but also their child. This symptom calls for immediate intervention and sometimes can be a sign of postpartum psychosis.

Postpartum psychosis is rare, occurring in about 1-3 out of 1,000 women, but its seriousness requires immediate medical attention, including hospitalization in most cases. The best established risk factor is preexisting bipolar disorder. Postpartum psychosis usually occurs in the first 4 weeks after delivery, with symptoms that include paranoia, severe mood shifts, hallucinations, delusions, and suicidal and/or homicidal thoughts.

Fathers also can experience depression after a baby’s birth: An estimated 6% of fathers develop paternal depression, but the numbers are triple that among fathers whose children are enrolled in Early Head Start programs, Dr. Bauer said. Paternal depression often co-occurs with postpartum maternal depression, particularly when poverty and substance abuse are contributing factors.

Fewer practitioners may be aware of postpartum anxiety disorders, even though they affect 9%-30% of women. These disorders include generalized anxiety disorder, OCD, and PTSD, either as a preexisting diagnosis or occurring after delivery. Women develop an intensive fear about their child’s well-being and worry that they aren’t able to parent adequately or effectively (Zero to Three. 2009 May:1-6).

Your role in screening mothers

It’s essential that you screen parents for depression, particularly mothers for PPD, because of the potential negative consequences for the child. Research has shown that children of mothers with PPD are at risk for failure to thrive, and have a greater likelihood of mental health conditions, developmental delays, lower IQ scores, sleep problems, and difficulties at school (Infant Behav Dev. 2011 Feb;34[1]:1-14). Further, mothers with PPD are less likely to breastfeed and more likely to stop breastfeeding early, studies have shown (Arch Pediatr Adolesc Med. 2006 Mar;160[3]:279-84).

The risk factors for PPD often occur together, with each additional one adding to the overall risk. As incidence estimates show, teens and those with low income are at higher risk, as are those with less education and any type of additional financial hardship. Other factors that increase women’s risk include interpersonal violence, a lack of social support, a history or family history of anxiety or depression, poor physical or mental health in general, and substance abuse (Depress Anxiety. 2017 Feb;34[2]:178-87).

Screening tools and procedures

Despite the risks to infants from maternal depression, less than half of pediatricians screen mothers for PPD, Dr. Bauer said. American Academy of Pediatrics surveys of 778 pediatricians in 2004 and 2013 found that the proportion of pediatricians screening or asking mothers about depression increased from 33% to 44% during that decade, driven partly by the “belief that family screening is in the scope of practice,” she explained. Physicians who asked about the child’s mood were more likely to ask mothers about their mood too, the surveys found (J Dev Behav Pediatr. 2016 Feb-Mar;37[2]:113-20).

Medical organizations differ in their screening recommendations, although all agree screening is important. The American College of Obstetricians and Gynecologists and the U.S. Preventive Services Task Force recommend screening mothers at least once in the perinatal period (Obstet Gynecol. 2015;125:1268–71; JAMA. 2016;315[4]:388-406). The AAP advocates a more aggressive approach, recommending screening at each of the 1, 2, 4, and 6-month child well-visits (“Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents,” 4th Edition [Elk Grove Village, Ill.: American Academy of Pediatrics Publishing, 2017]).

The two preferred screening tools for PPD are the Edinburgh Postpartum Depression Scale (EPDS) and the Patient Health Questionnaire (PHQ).

The former is fast and simple, requiring less than 5 minutes for mothers to answer 10 items about their symptoms in the previous 7 days. The EPDS has a maximum score of 30; anything above 12-13 should prompt further examination or referral. Women scoring a 10 should be reassessed 2 weeks later, unless they answer affirmatively to item 10 on suicidal ideation, in which case they should be referred immediately.

You also can use a shortened form of the EPDS as a first step, asking about the three EPDS items related to anxiety: “self-blame, feeling panicky, and [feeling] anxious or worried for no good reason,” Dr. Bauer said, explaining “the score should be multiplied by 10 and divided by 3, so the cutoff is greater than or equal to 10.”

The PHQ-9 asks about symptoms in the previous 2 weeks. Scores of 10-14 indicate minor depression or mild major depression, and scores of 15-19 indicate moderate depression. Mothers require intervention if they score at least 20, or in the case of teenage mothers, if they score at least 11 or have suicidal thoughts. Like the shortened EPDS-3, the PHQ has a shortened two-question option you can use as surveillance before fully screening mothers: 1. Have you felt down, depressed, or hopeless in the past 2 weeks? 2. Have you felt little interest or pleasure in doing things in the past 2 weeks?

If mothers have a positive screen, Dr. Bauer recommended that practices document it, according to protocols they’ve already set up.

“It’s not unlike domestic violence, maternal substance abuse, or parental smoking habits,” she said. “The score need not be noted, but [should] include details such as the name of the screener used, interpretation of the results, and when a referral was made.”

After making a referral to her ob.gyn. or a mental health professional, you can continue to help mothers by offering support and reassurance, reminding them that they are not alone and not to blame for depression, and that treatment can help them. Encourage parents to seek your advice and support as a pediatrician and use you as a resource to refer them to services that can help, such as lactation consultants and home-visiting programs.

Dr. Bauer offerred the following recommendations for clinical practice:

• Choose a validated screener for postpartum depression.
• Share the tool with everyone in your practice.
• Identify ways to integrate the screening tool into daily work flow.
• Collect data.
• Implement and assess how it went after a short time, using plan-do-study-act cycles.

Dr. Bauer advised consulting the following websites for information regarding postpartum depression:

• AAP Screening and Technical Assistance and Resource (STAR) Center. This AAP website recommends validated screening tools for maternal depression and has them available on the site ().
• Postpartum Support International (PSI). This website offers information and resources for women, family, and professionals (). PSI can also be reached by calling 800-944-4773.
• PSI Support Coordinator Network. This network can provide referrals for specialized support, such as for members of the military, for fathers, when there are legal concerns, or when psychosis is present, and serves all 50 states and 40 countries ().
• PostpartumDads. This website has recommendations for partners of women with postpartum depression, offering recommendations on how dads can help themselves and the mothers ().

Dr. Bauer said she had no relevant financial disclosures. She reported that her spouse is an employee of Anthem and holds Anthem stocks/bonds. No external funding was used for the presentation.

CHICAGO – Screening mothers for postpartum depression is critical, because of the potential negative consequences for the child, according to Nerissa S. Bauer, MD, MPH.

Postpartum depression is the best known mood disorder related to pregnancy, but it’s not the only one. Perinatal mood and anxiety disorders exist along a spectrum, she told attendees at the American Academy of Pediatrics annual meeting. That spectrum includes prenatal depression, prenatal anxiety, “baby blues,” postpartum depression, posttraumatic stress disorder (PSTD), and postpartum anxiety with panic attacks and/or obsessive-compulsive disorder (OCD).

monkeybusinessimages/Thinkstock

Postpartum mood disorders

Postpartum depression (PPD), however, is serious and requires intervention. An estimated 10%-20% of new mothers experience PPD, but the numbers are much higher in at-risk communities. Up to 48% of mothers in low-income households and 40%-60% of adolescent mothers in low-income households experience it. Yet only about 15% of these higher-risk women seek treatment for PPD (Pediatrics. 2010 Nov;126[5]:1032-9).

PPD symptoms are similar to the usual symptoms of a depressive disorder: depressed mood, irritability, changes in sleep and/or appetite, fatigue, sleepiness, loss of interest in activities, inability to feel pleasure in everyday life, guilt, difficulty concentrating, indecisiveness, low energy, despair, and feelings of worthlessness. The biggest difference – and most important symptom – is that women with PPD may have thoughts about harming not only themselves but also their child. This symptom calls for immediate intervention and sometimes can be a sign of postpartum psychosis.

Postpartum psychosis is rare, occurring in about 1-3 out of 1,000 women, but its seriousness requires immediate medical attention, including hospitalization in most cases. The best established risk factor is preexisting bipolar disorder. Postpartum psychosis usually occurs in the first 4 weeks after delivery, with symptoms that include paranoia, severe mood shifts, hallucinations, delusions, and suicidal and/or homicidal thoughts.

Fathers also can experience depression after a baby’s birth: An estimated 6% of fathers develop paternal depression, but the numbers are triple that among fathers whose children are enrolled in Early Head Start programs, Dr. Bauer said. Paternal depression often co-occurs with postpartum maternal depression, particularly when poverty and substance abuse are contributing factors.

Fewer practitioners may be aware of postpartum anxiety disorders, even though they affect 9%-30% of women. These disorders include generalized anxiety disorder, OCD, and PTSD, either as a preexisting diagnosis or occurring after delivery. Women develop an intensive fear about their child’s well-being and worry that they aren’t able to parent adequately or effectively (Zero to Three. 2009 May:1-6).

Your role in screening mothers

It’s essential that you screen parents for depression, particularly mothers for PPD, because of the potential negative consequences for the child. Research has shown that children of mothers with PPD are at risk for failure to thrive, and have a greater likelihood of mental health conditions, developmental delays, lower IQ scores, sleep problems, and difficulties at school (Infant Behav Dev. 2011 Feb;34[1]:1-14). Further, mothers with PPD are less likely to breastfeed and more likely to stop breastfeeding early, studies have shown (Arch Pediatr Adolesc Med. 2006 Mar;160[3]:279-84).

The risk factors for PPD often occur together, with each additional one adding to the overall risk. As incidence estimates show, teens and those with low income are at higher risk, as are those with less education and any type of additional financial hardship. Other factors that increase women’s risk include interpersonal violence, a lack of social support, a history or family history of anxiety or depression, poor physical or mental health in general, and substance abuse (Depress Anxiety. 2017 Feb;34[2]:178-87).

Screening tools and procedures

Despite the risks to infants from maternal depression, less than half of pediatricians screen mothers for PPD, Dr. Bauer said. American Academy of Pediatrics surveys of 778 pediatricians in 2004 and 2013 found that the proportion of pediatricians screening or asking mothers about depression increased from 33% to 44% during that decade, driven partly by the “belief that family screening is in the scope of practice,” she explained. Physicians who asked about the child’s mood were more likely to ask mothers about their mood too, the surveys found (J Dev Behav Pediatr. 2016 Feb-Mar;37[2]:113-20).

Medical organizations differ in their screening recommendations, although all agree screening is important. The American College of Obstetricians and Gynecologists and the U.S. Preventive Services Task Force recommend screening mothers at least once in the perinatal period (Obstet Gynecol. 2015;125:1268–71; JAMA. 2016;315[4]:388-406). The AAP advocates a more aggressive approach, recommending screening at each of the 1, 2, 4, and 6-month child well-visits (“Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents,” 4th Edition [Elk Grove Village, Ill.: American Academy of Pediatrics Publishing, 2017]).

The two preferred screening tools for PPD are the Edinburgh Postpartum Depression Scale (EPDS) and the Patient Health Questionnaire (PHQ).

The former is fast and simple, requiring less than 5 minutes for mothers to answer 10 items about their symptoms in the previous 7 days. The EPDS has a maximum score of 30; anything above 12-13 should prompt further examination or referral. Women scoring a 10 should be reassessed 2 weeks later, unless they answer affirmatively to item 10 on suicidal ideation, in which case they should be referred immediately.

You also can use a shortened form of the EPDS as a first step, asking about the three EPDS items related to anxiety: “self-blame, feeling panicky, and [feeling] anxious or worried for no good reason,” Dr. Bauer said, explaining “the score should be multiplied by 10 and divided by 3, so the cutoff is greater than or equal to 10.”

The PHQ-9 asks about symptoms in the previous 2 weeks. Scores of 10-14 indicate minor depression or mild major depression, and scores of 15-19 indicate moderate depression. Mothers require intervention if they score at least 20, or in the case of teenage mothers, if they score at least 11 or have suicidal thoughts. Like the shortened EPDS-3, the PHQ has a shortened two-question option you can use as surveillance before fully screening mothers: 1. Have you felt down, depressed, or hopeless in the past 2 weeks? 2. Have you felt little interest or pleasure in doing things in the past 2 weeks?

If mothers have a positive screen, Dr. Bauer recommended that practices document it, according to protocols they’ve already set up.

“It’s not unlike domestic violence, maternal substance abuse, or parental smoking habits,” she said. “The score need not be noted, but [should] include details such as the name of the screener used, interpretation of the results, and when a referral was made.”

After making a referral to her ob.gyn. or a mental health professional, you can continue to help mothers by offering support and reassurance, reminding them that they are not alone and not to blame for depression, and that treatment can help them. Encourage parents to seek your advice and support as a pediatrician and use you as a resource to refer them to services that can help, such as lactation consultants and home-visiting programs.

Dr. Bauer offerred the following recommendations for clinical practice:

• Choose a validated screener for postpartum depression.
• Share the tool with everyone in your practice.
• Identify ways to integrate the screening tool into daily work flow.
• Collect data.
• Implement and assess how it went after a short time, using plan-do-study-act cycles.

Dr. Bauer advised consulting the following websites for information regarding postpartum depression:

• AAP Screening and Technical Assistance and Resource (STAR) Center. This AAP website recommends validated screening tools for maternal depression and has them available on the site ().
• Postpartum Support International (PSI). This website offers information and resources for women, family, and professionals (). PSI can also be reached by calling 800-944-4773.
• PSI Support Coordinator Network. This network can provide referrals for specialized support, such as for members of the military, for fathers, when there are legal concerns, or when psychosis is present, and serves all 50 states and 40 countries ().
• PostpartumDads. This website has recommendations for partners of women with postpartum depression, offering recommendations on how dads can help themselves and the mothers ().

Dr. Bauer said she had no relevant financial disclosures. She reported that her spouse is an employee of Anthem and holds Anthem stocks/bonds. No external funding was used for the presentation.

CHICAGO – Screening mothers for postpartum depression is critical, because of the potential negative consequences for the child, according to Nerissa S. Bauer, MD, MPH.

Postpartum depression is the best known mood disorder related to pregnancy, but it’s not the only one. Perinatal mood and anxiety disorders exist along a spectrum, she told attendees at the American Academy of Pediatrics annual meeting. That spectrum includes prenatal depression, prenatal anxiety, “baby blues,” postpartum depression, posttraumatic stress disorder (PSTD), and postpartum anxiety with panic attacks and/or obsessive-compulsive disorder (OCD).

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Postpartum mood disorders

Postpartum depression (PPD), however, is serious and requires intervention. An estimated 10%-20% of new mothers experience PPD, but the numbers are much higher in at-risk communities. Up to 48% of mothers in low-income households and 40%-60% of adolescent mothers in low-income households experience it. Yet only about 15% of these higher-risk women seek treatment for PPD (Pediatrics. 2010 Nov;126[5]:1032-9).

PPD symptoms are similar to the usual symptoms of a depressive disorder: depressed mood, irritability, changes in sleep and/or appetite, fatigue, sleepiness, loss of interest in activities, inability to feel pleasure in everyday life, guilt, difficulty concentrating, indecisiveness, low energy, despair, and feelings of worthlessness. The biggest difference – and most important symptom – is that women with PPD may have thoughts about harming not only themselves but also their child. This symptom calls for immediate intervention and sometimes can be a sign of postpartum psychosis.

Postpartum psychosis is rare, occurring in about 1-3 out of 1,000 women, but its seriousness requires immediate medical attention, including hospitalization in most cases. The best established risk factor is preexisting bipolar disorder. Postpartum psychosis usually occurs in the first 4 weeks after delivery, with symptoms that include paranoia, severe mood shifts, hallucinations, delusions, and suicidal and/or homicidal thoughts.

Fathers also can experience depression after a baby’s birth: An estimated 6% of fathers develop paternal depression, but the numbers are triple that among fathers whose children are enrolled in Early Head Start programs, Dr. Bauer said. Paternal depression often co-occurs with postpartum maternal depression, particularly when poverty and substance abuse are contributing factors.

Fewer practitioners may be aware of postpartum anxiety disorders, even though they affect 9%-30% of women. These disorders include generalized anxiety disorder, OCD, and PTSD, either as a preexisting diagnosis or occurring after delivery. Women develop an intensive fear about their child’s well-being and worry that they aren’t able to parent adequately or effectively (Zero to Three. 2009 May:1-6).

Your role in screening mothers

It’s essential that you screen parents for depression, particularly mothers for PPD, because of the potential negative consequences for the child. Research has shown that children of mothers with PPD are at risk for failure to thrive, and have a greater likelihood of mental health conditions, developmental delays, lower IQ scores, sleep problems, and difficulties at school (Infant Behav Dev. 2011 Feb;34[1]:1-14). Further, mothers with PPD are less likely to breastfeed and more likely to stop breastfeeding early, studies have shown (Arch Pediatr Adolesc Med. 2006 Mar;160[3]:279-84).

The risk factors for PPD often occur together, with each additional one adding to the overall risk. As incidence estimates show, teens and those with low income are at higher risk, as are those with less education and any type of additional financial hardship. Other factors that increase women’s risk include interpersonal violence, a lack of social support, a history or family history of anxiety or depression, poor physical or mental health in general, and substance abuse (Depress Anxiety. 2017 Feb;34[2]:178-87).

Screening tools and procedures

Despite the risks to infants from maternal depression, less than half of pediatricians screen mothers for PPD, Dr. Bauer said. American Academy of Pediatrics surveys of 778 pediatricians in 2004 and 2013 found that the proportion of pediatricians screening or asking mothers about depression increased from 33% to 44% during that decade, driven partly by the “belief that family screening is in the scope of practice,” she explained. Physicians who asked about the child’s mood were more likely to ask mothers about their mood too, the surveys found (J Dev Behav Pediatr. 2016 Feb-Mar;37[2]:113-20).

Medical organizations differ in their screening recommendations, although all agree screening is important. The American College of Obstetricians and Gynecologists and the U.S. Preventive Services Task Force recommend screening mothers at least once in the perinatal period (Obstet Gynecol. 2015;125:1268–71; JAMA. 2016;315[4]:388-406). The AAP advocates a more aggressive approach, recommending screening at each of the 1, 2, 4, and 6-month child well-visits (“Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents,” 4th Edition [Elk Grove Village, Ill.: American Academy of Pediatrics Publishing, 2017]).

The two preferred screening tools for PPD are the Edinburgh Postpartum Depression Scale (EPDS) and the Patient Health Questionnaire (PHQ).

The former is fast and simple, requiring less than 5 minutes for mothers to answer 10 items about their symptoms in the previous 7 days. The EPDS has a maximum score of 30; anything above 12-13 should prompt further examination or referral. Women scoring a 10 should be reassessed 2 weeks later, unless they answer affirmatively to item 10 on suicidal ideation, in which case they should be referred immediately.

You also can use a shortened form of the EPDS as a first step, asking about the three EPDS items related to anxiety: “self-blame, feeling panicky, and [feeling] anxious or worried for no good reason,” Dr. Bauer said, explaining “the score should be multiplied by 10 and divided by 3, so the cutoff is greater than or equal to 10.”

The PHQ-9 asks about symptoms in the previous 2 weeks. Scores of 10-14 indicate minor depression or mild major depression, and scores of 15-19 indicate moderate depression. Mothers require intervention if they score at least 20, or in the case of teenage mothers, if they score at least 11 or have suicidal thoughts. Like the shortened EPDS-3, the PHQ has a shortened two-question option you can use as surveillance before fully screening mothers: 1. Have you felt down, depressed, or hopeless in the past 2 weeks? 2. Have you felt little interest or pleasure in doing things in the past 2 weeks?

If mothers have a positive screen, Dr. Bauer recommended that practices document it, according to protocols they’ve already set up.

“It’s not unlike domestic violence, maternal substance abuse, or parental smoking habits,” she said. “The score need not be noted, but [should] include details such as the name of the screener used, interpretation of the results, and when a referral was made.”

After making a referral to her ob.gyn. or a mental health professional, you can continue to help mothers by offering support and reassurance, reminding them that they are not alone and not to blame for depression, and that treatment can help them. Encourage parents to seek your advice and support as a pediatrician and use you as a resource to refer them to services that can help, such as lactation consultants and home-visiting programs.

Dr. Bauer offerred the following recommendations for clinical practice:

• Choose a validated screener for postpartum depression.
• Share the tool with everyone in your practice.
• Identify ways to integrate the screening tool into daily work flow.
• Collect data.
• Implement and assess how it went after a short time, using plan-do-study-act cycles.

Dr. Bauer advised consulting the following websites for information regarding postpartum depression:

• AAP Screening and Technical Assistance and Resource (STAR) Center. This AAP website recommends validated screening tools for maternal depression and has them available on the site ().
• Postpartum Support International (PSI). This website offers information and resources for women, family, and professionals (). PSI can also be reached by calling 800-944-4773.
• PSI Support Coordinator Network. This network can provide referrals for specialized support, such as for members of the military, for fathers, when there are legal concerns, or when psychosis is present, and serves all 50 states and 40 countries ().
• PostpartumDads. This website has recommendations for partners of women with postpartum depression, offering recommendations on how dads can help themselves and the mothers ().

Dr. Bauer said she had no relevant financial disclosures. She reported that her spouse is an employee of Anthem and holds Anthem stocks/bonds. No external funding was used for the presentation.

Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.

“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.

In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
 

Price tag pressure

During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.

Cost-saving proposals

Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.

Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.

In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.

“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.

In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.

In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.

“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.

The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.

Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).

“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.

The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.

Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.

“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”

Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.

[email protected]

Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.

“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.

In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
 

Price tag pressure

During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.

Cost-saving proposals

Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.

Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.

In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.

“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.

In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.

In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.

“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.

The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.

Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).

“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.

The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.

Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.

“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”

Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.

[email protected]

Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.

“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.

In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
 

Price tag pressure

During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.

Cost-saving proposals

Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.

Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.

In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.

“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.

In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.

In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.

“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.

The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.

Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).

“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.

The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.

Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.

“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”

Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.

[email protected]

MONTREAL – Have restrictions on scope of practice contributed to primary care physician burnout?

Perhaps they have, according to a recent survey that saw less burnout among recently graduated family physicians who retained inpatient or obstetrics work.

Of the 1,167 family practice physicians surveyed, 42% reported that they felt burned out once per week or more, said Amanda Weidner, MPH, of the University of Washington Family Medicine Residency Network in Seattle. However, some physicians were significantly less likely to experience burnout: those whose practice included adult inpatient medicine (P less than .0001), those currently delivering babies (P = .0007), and those who routinely saw their patients at the hospital or in patients’ homes (P = .0016 and P = .02, respectively).

Kari Oakes/Frontline Medical News

[email protected]

On Twitter @karioakes

MONTREAL – Have restrictions on scope of practice contributed to primary care physician burnout?

Perhaps they have, according to a recent survey that saw less burnout among recently graduated family physicians who retained inpatient or obstetrics work.

Of the 1,167 family practice physicians surveyed, 42% reported that they felt burned out once per week or more, said Amanda Weidner, MPH, of the University of Washington Family Medicine Residency Network in Seattle. However, some physicians were significantly less likely to experience burnout: those whose practice included adult inpatient medicine (P less than .0001), those currently delivering babies (P = .0007), and those who routinely saw their patients at the hospital or in patients’ homes (P = .0016 and P = .02, respectively).

Kari Oakes/Frontline Medical News

[email protected]

On Twitter @karioakes

MONTREAL – Have restrictions on scope of practice contributed to primary care physician burnout?

Perhaps they have, according to a recent survey that saw less burnout among recently graduated family physicians who retained inpatient or obstetrics work.

Of the 1,167 family practice physicians surveyed, 42% reported that they felt burned out once per week or more, said Amanda Weidner, MPH, of the University of Washington Family Medicine Residency Network in Seattle. However, some physicians were significantly less likely to experience burnout: those whose practice included adult inpatient medicine (P less than .0001), those currently delivering babies (P = .0007), and those who routinely saw their patients at the hospital or in patients’ homes (P = .0016 and P = .02, respectively).

Kari Oakes/Frontline Medical News

[email protected]

On Twitter @karioakes

ADHD is a very common disorder with several medication treatment options. There also are wellness and parenting strategies that can address aspects of the challenges of ADHD that are not perfectly covered by medication, such as excess symptoms, times of day that are not covered, or oppositional behavior that often develops secondarily.

Case summary

James is a 6-year-old boy who has been an active, high-energy child since preschool. He has had difficulty with wiggling around in kindergarten and preschool, talking excessively, and being unable to follow directions and pay attention. He is impulsive, disruptive, and frequently doesn’t listen to what his parents tell him to do. Parents and teachers rank him in the clinical range for hyperactivity, impulsivity, and attention problems on standardized rating scales.

Discussion

When we first discuss a new diagnosis with a family, we have the opportunity to shape the family’s expectations about that diagnosis and how it should be addressed. When I discuss ADHD with a new family, I want them to understand the symptoms of inattention, hyperactivity, and impulsiveness, and that these symptoms are not the child’s fault, but rather related to the way his brain is connected. At the same time, I also emphasize that these connections are not entirely fixed, that they mature over time, and that they are affected by experiences in life. In particular, I stress that positive experiences and wellness activities can influence the brain in a positive way. While, of course, I discuss the range of medications that can address these issues, I also deal with wellness in the treatment plan.

monkeybusinessimages/Thinkstock

Exercise

Studies in humans and animals have provided background evidence that exercise increases the release of neurotransmitters such as dopamine and norepinephrine that are important in the pathophysiology of ADHD. Cerillo-Urbina et al. did a meta-analysis in 2015 of randomized controlled trials and found medium to large effect sizes for a variety of physical activity programs with respect to attention, hyperactivity, and impulsivity, although the study quality was generally low.¹ Clearly we need additional more rigorous studies, but given the positive direction of outcomes, the lack of side effects, and the many other positive effects of exercise, it does not seem too soon to add exercise as a prescription for our patients with ADHD. I review this evidence with families, ask them about physical activity they like, and ask if they are willing to work toward an hour of exercise a day.

Sleep

Many children with ADHD have problems with sleep even before they start on stimulant medications, which can further affect sleep. Addressing sleep early on can improve ADHD symptoms, as well as help parents change or avoid patterns like having children fall asleep to the sound of a television. Brief sleep hygiene and cognitive-behavioral therapy interventions over three visits were demonstrated in a randomized controlled trial by Hisock et al. to improve ADHD symptoms and behavioral function.² These psychosocial interventions clearly are the first line in addressing sleep problems in ADHD, and can benefit even sleep problems connected to medication.

Parent training

Treatment plan

1. Have the child exercise 1 hour every day. Have fun!

2. Establish a nightly bedtime routine, with a bath at 7:30 p.m., brushing of teeth, a story, and lights out at 8 with no TV in the room.

3. Check out the CHADD website for Parent to Parent.

4. Start a trial of stimulant medication.

5. Return in 2 weeks to monitor these interventions, adjust goals, and adjust medications.

When to refer

Many parents will be able to put such a plan in motion with your support and that of other parents. If they are struggling, therapists, psychologists, and psychiatrists trained in motivational and behavioral methods can provide more individualized parent training. Also consider whether the parents themselves may have ADHD and could use referral and treatment.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

References

1. Child Care Health Dev. 2015 Nov;41(6):779-88.

2. BMJ. 2015. doi: 10.1136/bmj.h68.

ADHD is a very common disorder with several medication treatment options. There also are wellness and parenting strategies that can address aspects of the challenges of ADHD that are not perfectly covered by medication, such as excess symptoms, times of day that are not covered, or oppositional behavior that often develops secondarily.

Case summary

James is a 6-year-old boy who has been an active, high-energy child since preschool. He has had difficulty with wiggling around in kindergarten and preschool, talking excessively, and being unable to follow directions and pay attention. He is impulsive, disruptive, and frequently doesn’t listen to what his parents tell him to do. Parents and teachers rank him in the clinical range for hyperactivity, impulsivity, and attention problems on standardized rating scales.

Discussion

When we first discuss a new diagnosis with a family, we have the opportunity to shape the family’s expectations about that diagnosis and how it should be addressed. When I discuss ADHD with a new family, I want them to understand the symptoms of inattention, hyperactivity, and impulsiveness, and that these symptoms are not the child’s fault, but rather related to the way his brain is connected. At the same time, I also emphasize that these connections are not entirely fixed, that they mature over time, and that they are affected by experiences in life. In particular, I stress that positive experiences and wellness activities can influence the brain in a positive way. While, of course, I discuss the range of medications that can address these issues, I also deal with wellness in the treatment plan.

monkeybusinessimages/Thinkstock

Exercise

Studies in humans and animals have provided background evidence that exercise increases the release of neurotransmitters such as dopamine and norepinephrine that are important in the pathophysiology of ADHD. Cerillo-Urbina et al. did a meta-analysis in 2015 of randomized controlled trials and found medium to large effect sizes for a variety of physical activity programs with respect to attention, hyperactivity, and impulsivity, although the study quality was generally low.¹ Clearly we need additional more rigorous studies, but given the positive direction of outcomes, the lack of side effects, and the many other positive effects of exercise, it does not seem too soon to add exercise as a prescription for our patients with ADHD. I review this evidence with families, ask them about physical activity they like, and ask if they are willing to work toward an hour of exercise a day.

Sleep

Many children with ADHD have problems with sleep even before they start on stimulant medications, which can further affect sleep. Addressing sleep early on can improve ADHD symptoms, as well as help parents change or avoid patterns like having children fall asleep to the sound of a television. Brief sleep hygiene and cognitive-behavioral therapy interventions over three visits were demonstrated in a randomized controlled trial by Hisock et al. to improve ADHD symptoms and behavioral function.² These psychosocial interventions clearly are the first line in addressing sleep problems in ADHD, and can benefit even sleep problems connected to medication.

Parent training

Treatment plan

1. Have the child exercise 1 hour every day. Have fun!

2. Establish a nightly bedtime routine, with a bath at 7:30 p.m., brushing of teeth, a story, and lights out at 8 with no TV in the room.

3. Check out the CHADD website for Parent to Parent.

4. Start a trial of stimulant medication.

5. Return in 2 weeks to monitor these interventions, adjust goals, and adjust medications.

When to refer

Many parents will be able to put such a plan in motion with your support and that of other parents. If they are struggling, therapists, psychologists, and psychiatrists trained in motivational and behavioral methods can provide more individualized parent training. Also consider whether the parents themselves may have ADHD and could use referral and treatment.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

References

1. Child Care Health Dev. 2015 Nov;41(6):779-88.

2. BMJ. 2015. doi: 10.1136/bmj.h68.

ADHD is a very common disorder with several medication treatment options. There also are wellness and parenting strategies that can address aspects of the challenges of ADHD that are not perfectly covered by medication, such as excess symptoms, times of day that are not covered, or oppositional behavior that often develops secondarily.

Case summary

James is a 6-year-old boy who has been an active, high-energy child since preschool. He has had difficulty with wiggling around in kindergarten and preschool, talking excessively, and being unable to follow directions and pay attention. He is impulsive, disruptive, and frequently doesn’t listen to what his parents tell him to do. Parents and teachers rank him in the clinical range for hyperactivity, impulsivity, and attention problems on standardized rating scales.

Discussion

When we first discuss a new diagnosis with a family, we have the opportunity to shape the family’s expectations about that diagnosis and how it should be addressed. When I discuss ADHD with a new family, I want them to understand the symptoms of inattention, hyperactivity, and impulsiveness, and that these symptoms are not the child’s fault, but rather related to the way his brain is connected. At the same time, I also emphasize that these connections are not entirely fixed, that they mature over time, and that they are affected by experiences in life. In particular, I stress that positive experiences and wellness activities can influence the brain in a positive way. While, of course, I discuss the range of medications that can address these issues, I also deal with wellness in the treatment plan.

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Exercise

Studies in humans and animals have provided background evidence that exercise increases the release of neurotransmitters such as dopamine and norepinephrine that are important in the pathophysiology of ADHD. Cerillo-Urbina et al. did a meta-analysis in 2015 of randomized controlled trials and found medium to large effect sizes for a variety of physical activity programs with respect to attention, hyperactivity, and impulsivity, although the study quality was generally low.¹ Clearly we need additional more rigorous studies, but given the positive direction of outcomes, the lack of side effects, and the many other positive effects of exercise, it does not seem too soon to add exercise as a prescription for our patients with ADHD. I review this evidence with families, ask them about physical activity they like, and ask if they are willing to work toward an hour of exercise a day.

Sleep

Many children with ADHD have problems with sleep even before they start on stimulant medications, which can further affect sleep. Addressing sleep early on can improve ADHD symptoms, as well as help parents change or avoid patterns like having children fall asleep to the sound of a television. Brief sleep hygiene and cognitive-behavioral therapy interventions over three visits were demonstrated in a randomized controlled trial by Hisock et al. to improve ADHD symptoms and behavioral function.² These psychosocial interventions clearly are the first line in addressing sleep problems in ADHD, and can benefit even sleep problems connected to medication.

Parent training

Treatment plan

1. Have the child exercise 1 hour every day. Have fun!

2. Establish a nightly bedtime routine, with a bath at 7:30 p.m., brushing of teeth, a story, and lights out at 8 with no TV in the room.

3. Check out the CHADD website for Parent to Parent.

4. Start a trial of stimulant medication.

5. Return in 2 weeks to monitor these interventions, adjust goals, and adjust medications.

When to refer

Many parents will be able to put such a plan in motion with your support and that of other parents. If they are struggling, therapists, psychologists, and psychiatrists trained in motivational and behavioral methods can provide more individualized parent training. Also consider whether the parents themselves may have ADHD and could use referral and treatment.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

References

1. Child Care Health Dev. 2015 Nov;41(6):779-88.

2. BMJ. 2015. doi: 10.1136/bmj.h68.